Thionyl Fluoride-Mediated One-Pot Substitutions and Reductions of Carboxylic Acids.

Thionyl fluoride (SOF) is an underutilized reagent that is yet to be extensively studied for its synthetic applications. We previously reported that it is a powerful reagent for both the rapid syntheses of acyl fluorides and for one-pot peptide couplings, but the full scope of these nucleophilic acyl substitutions had not been explored. Herein, we report one-pot thionyl fluoride-mediated syntheses of peptides and amides (35 examples, 45-99% yields) that were not explored in our previous study.

Halide-Accelerated Acyl Fluoride Formation Using Sulfuryl Fluoride.

Herein, we report a new one-pot sequential method for SOF-mediated nucleophilic acyl substitution reactions starting from carboxylic acids. A mechanistic study revealed that SOF-mediated acid activation proceeds via the anhydride, which is then converted to the corresponding acyl fluoride. Tetrabutylammonium chloride or bromide accelerate the formation of acyl fluoride.

New sulfuryl fluoride-derived alkylating reagents for the 1,1-dihydrofluoroalkylation of thiols.

Herein, we report a new method for the one-pot synthesis of 1,1-dihydrofluoroalkyl sulfides by bubbling sulfuryl fluoride (SOF) through a solution of the corresponding alcohol and thiol. The reaction proceeds through a new class of bis(1,1-dihydrofluoroalkyl) sulfate reagents, to afford the desired 1,1-dihydrofluoroalkyl sulfides in 55-90% isolated yields. The bis(1,1-dihydrofluoroalkyl) sulfates are highly chemoselective for thiol alkylation, and are unreactive with competing, unprotected nucleophiles, including amines, alcohols, and carboxylic acids.

Assessment of Putative PD-1/PD-L1 Inhibitors: Suggestions of an Alternative Mode of Action.

The programmed cell death protein 1 (PD-1) signaling axis is among the most important therapeutic targets in modern oncology. Aurigene Discovery Technologies Ltd. (Aurigene) has patented a series of peptidomimetic small molecules derived from the PD-1 protein sequence for use in targeting the interaction between PD-1 and its ligand, PD-L1.

Neuropsychological dysfunction in patients suffering from end-stage chronic obstructive pulmonary disease.

Few studies have examined the neuropsychological sequelae associated with end-stage pulmonary disease. Neuropsychological data are presented for 47 patients with end-stage chronic obstructive pulmonary disease (COPD) who were being evaluated as potential candidates for lung transplantation. Although patients exhibited a diversity of neurocognitive deficits, their highest frequencies of impairment were found on the Selective Reminding Test (SRT).

Activation of thyrotropin-releasing hormone gene expression in cultured fetal diencephalic neurons by differentiating agents.

The present studies were undertaken to investigate the effect of 5-bromo-2'-deoxyuridine (BrdU; 50 microM) or forskolin/3-isobutyl-1-methylxanthine (F/I; 10/500 microM) on TRH gene expression in cultured fetal diencephalic cells. BrdU as well as drugs such as F/I that raise intracellular cAMP levels had been previously termed differentiating agents because they cause morphological and functional differentiation of IMR-32 neuroblastoma cells. We postulated that neurons of fetal diencephalons may remain relatively undifferentiated in vitro and that this might be the reason for low or undetectable TRH production.

Thyrotropin-releasing hormone gene expression in cultured anterior pituitary cells: role of gender.

The present studies were undertaken to investigate the effect of gender on thyrotropin-releasing hormone (TRH) gene expression in cultured anterior pituitary (AP) cells. AP cells derived from 15-day-old male, female, or female pups that had been neonatally treated with testosterone propionate (TP), were cultured for up to 18 days in a modified DMEM/L-15 medium containing 10% fetal calf serum. TRH and AP hormones including GH, prolactin (PRL), luteinizing hormone (LH) and thyrotropin (TSH) were measured by RIA, proTRH mRNA was determined by in situ hybridization using a full-length riboprobe followed by quantification with a computer-assisted image analysis system.

Onset of pro-thyrotropin-releasing hormone gene expression in cultured rat anterior pituitary cells is expedited by dexamethasone.

The early onset of proTRH gene expression in anterior pituitary (AP) cells in culture and its regulation by dexamethasone (DEX) were investigated. AP cells derived from 15-day-old rats were cultured for up to 4 days in the presence or absence of 10(-7) M DEX. TRH peptide levels, which could be detected only after 3 days of culture in control cells, were detectable after 1 day in DEX-treated cells.

Thyrotropin-releasing hormone gene expression in the anterior pituitary. III. Stimulation by thyroid hormone: potentiation by glucocorticoids.

The present study was designed to investigate the effect of thyroid hormone on TRH gene expression in cultured anterior pituitary (AP) cells. AP cells derived from 15-day-old male rats were cultured for up to 14 days in Dulbecco's Modified Eagle's Medium-L-15 medium supplemented with either fetal calf serum (FCS) or FCS devoid of thyroid hormones. T4 or T3 were added at various concentrations to the medium for a duration of 2-14 days.

Thyrotropin-releasing hormone gene expression in the anterior pituitary. II. Stimulation by glucocorticoids.

The present studies were undertaken to determine whether glucocorticoids (GC) regulate TRH gene expression in cultured anterior pituitary (AP) cells. AP cells derived from 15-day-old male rats were cultured for up to 18 days in Dulbecco's Modified Eagle's Medium-L-15 medium supplemented with 1) fetal calf serum (FCS), 2) charcoal-treated FCS, 3) normal rat serum, or 4) serum from rats that were adrenalectomized, rendered hypothyroid, and gonadectomized (ATG rat serum). Dexamethasone (Dex) or corticosterone (Cort) was added to the culture medium at various concentrations with exposure times ranging from 4-18 days.

Thyrotropin-releasing hormone (TRH) gene expression in the anterior pituitary. I. Presence of pro-TRH messenger ribonucleic acid and pro-TRH-derived peptide in a subpopulation of somatotrophs.

We have previously reported the presence of authentic pro-TRH-derived peptides in cultured anterior pituitary (AP) cells. The present studies were undertaken to determine whether pro-TRH mRNA could be demonstrated in the AP and to elucidate the cell type expressing pro-TRH. AP cells were cultured for up to 18 days, during which time the content of both TRH and prepro-TRH-(25-50) rose significantly (P < 0.

Changes in brain gonadotropin-releasing hormone, plasma estradiol 17-beta, and progesterone during the final reproductive cycle of the female sea lamprey, Petromyzon marinus.

Changes in ovarian morphology, brain gonadotropin-releasing hormone (GnRH), plasma estradiol, and progesterone were examined during the 1988 and 1989 spawning migrations of the adult female sea lamprey, Petromyzon marinus. There were significant increases through time in brain GnRH (1989) and plasma estradiol (1988 and 1989), with progesterone levels fluctuating (1988 and 1989) during the freshwater phase of the spawning migrations. In 1989, brain GnRH and plasma estradiol levels gradually increased through time until just prior to spawning when levels decreased.

Protrh peptides are synthesized and secreted by anterior pituitary cells in long-term culture.

The expression of two ProTRH derived peptides, thyrotropin--releasing hormone (TRH) and PrePro-TRH25-50 (PYE27) was studied in anterior pituitary (AP) cells cultured in monolayer for up to 21 days. TRH levels in extracted cells rose from undetectable at 3 days to 267 +/- 22.5 fmol/well (p less than 0.